title: Genome-wide computational analysis of dioxin response element location and distribution in the human, mouse, and rat genomes.
abstract: The aryl hydrocarbon receptor (AhR) mediates responses elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin by binding to dioxin response elements (DRE) containing the core consensus sequence 5'-GCGTG-3'. The human, mouse, and rat genomes were computationally searched for all DRE cores. Each core was then extended by 7 bp upstream and downstream, and matrix similarity (MS) scores for the resulting 19 bp DRE sequences were calculated using a revised position weight matrix constructed from bona fide functional DREs. In total, 72318 human, 70720 mouse, and 88651 rat high-scoring (MS ≥ 0.8437) putative DREs were identified. Gene-encoding intragenic DNA regions had ∼1.6 times more putative DREs than the noncoding intergenic DNA regions. Furthermore, the promoter region spanning ±1.5 kb of a TSS had the highest density of putative DREs within the genome. Chromosomal analysis found that the putative DRE densities of chromosomes X and Y were significantly lower than the mean chromosomal density. Interestingly, the 10 kb upstream promoter region on chromosome X of the genomes were significantly less dense than the chromosomal mean, while the same region in chromosome Y was the most dense. In addition to providing a detailed genomic map of all DRE cores in the human, mouse, and rat genomes, these data will further aid the elucidation of AhR-mediated signal transduction.
authors.affiliation: Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Dere
authors.forename: Agnes L
authors.initials: AL
authors.lastname: Forgacs
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Zacharewski
authors.forename: Lyle D
authors.initials: LD
authors.lastname: Burgoon
mesh_terms: D000818:Animals; D001483:Base Sequence; D002875:Chromosomes; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D016678:Genome; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D008024:Ligands; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D000072317:Polychlorinated Dibenzodioxins / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D011401:Promoter Regions, Genetic; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D020218:Response Elements; D024363:Transcription Initiation Site
chemical_list: D008024:Ligands; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1